CKD

Question 1

Stages of CKD:

Answer 1

Stage 1: GFR>90+ other evidence of kidney damage (eg. proteinuria, PCKD)

Stage2:GFR 60-90+ other evidence of kidney damage

Stage 3:GFR 30-60+/- other evidence of kidney damage[Stage 3a = 45-60Stage 3b = 30-45]

Stage 4:GFR 15-30+/- other evidence of kidney damage

Stage 5:GFR <15Established renal failure

Question 2

Reflux-associated nephropathy. Aetiology of CKD in this setting?

Answer 2

Not due to reflux.
Congenital abnormalities underlie both the reflux and the kidney damage independently.
CKD results from renal maldevelopment (hypoplasia and dysplasia) associated with VUR.
It is now thought that VUR does not play a role in renal scar formation and potential chronic kidney disease (CKD) but is a marker for abnormal renal development, which results in decreased formation of renal parenchyma referred to as primary renal scarring.

Question 3

Associations with ADPKD?Locations of cysts?

Answer 3

Cysts: kidney, liver, gut, pancreas.
Aortic and intracranial aneurysms.
Heart valve defects.
Recurrent UTIs and renal stones.

Question 4

Best test to rule out PCKD?

Answer 4

This is talking about autosomal dominant PCKD.

Renal USS (for cysts) - in an adult. But in the paediatric population, if a patient doesn’t have cysts, that does NOT exclude future cysts.

Genetic mutation analysis would be better, but would need to know exact mutation of proband (usually don’t).

Question 5

Mechanism of ACEi in Tx of proteinuria?

Answer 5

Decreased glomerular filtration pressure due to affect on angiotensin (ie. decreased single nephron GFR).

Also change in podocyte behaviour contributes.

Question 6

Cause of renal anaemia?

Answer 6

EPO deficiency due to decreased production:

But usually not apparent until GFR t require EPO as still produce.]

Beware low Hb in patient with mild to mod CKD:- GI bleeding common (possible clue: urea rise out of proportion to rise in Cr)

• Other causes for bleeding possible: eg. BM abnormality,
  fibrosis assoc. with hyperPTH in advanced CKD.
• Look for iron deficiency: should NOT find in stages 1-3a CKD. Ability to absorb iron from gut decreases with progressive CKD, but usually still enough until EPO replacement begins (unless bleeding).

Once on EPO - require iron supplementation (aim ferritin ~200).

Question 7

Target Hb in CKD and ESRD patients?

Answer 7

Dialysis patients: Hb 110-120 approx.

Possibly lower in CKD patients (roughly 100-110)Note: aiming for higher levels seems to increase morbidity and mortality (strokes, VTE, cardiac events), even if don’t reach target levels.

Question 8

Erythropoeitin replacement products:

Answer 8

Weekly dosing:- Epprex (Erythropoeitin alpha)- Neorecormon (Erythropoeitin beta)

Fortnightly dosing:- Aranesp (Darbopoeitin)

Monthly dosing (after fortnightly loading period):Mircera (EPO RECEPTOR ACTIVATOR - not EPO replacement).

Question 9

Understanding CKD-MBD (Chronic Kidney Disease - Mineral and Bone Disease).

What drives the PTH up?

Answer 9

High phosphate and low calcium (initially), until tertiary hyper PTH develops.
___________________

Hyperphosphataemia due to inadequate excretion (may still have normal serum levels initially; see in stages 1-3a)

Hypocalcaemia due to

• inadequate gut absorption of calcium
• inadequate active vit D (1,25-OH2 vitD)
• may also have low 25-OH vitD (because they stay out of sun)

Vitamin D deficiency (reduced production).

Both hyperphosphataemia and hypocalcaemia cause hyperparathyroidism

HyperPTH may normalise calcium to some extent = SECONDARY hyperparathyroidism (phosphate will still be elevated).

Eventually PTH glands become autonomous due to hyperplasia = TERTIARY hyperparathyroidism –> hypercalcaemia develops (at expense of the bones).

High calcium + high phosphate –> high calcium/phosphate product –> deposited in vessel walls, etc.

Question 10

Treatment of hyperphosphataemia in CKD?What is the target?

Answer 10

1. Low-phosphate diet (note: high in coke and sodium phosphate in fast food!)
2. Phosphate binders - this is the most effective way to treat hyperphos in CKD
3. RRT

Target:- normal range in early CKD- as CKD advances aim <1.8 (preferably ~1.6)

Question 11

Treatment of hypocalcaemia in CKD?

What is the target?

Answer 11

Calcitriol: increases absorption of calcium from gut and resorption from bone.

Target: normocalcaemia (ionised calcium)

Note: if on caltrate it is as a phosphate binder, NOT for hypocalcaemia! -hypocalcaemia is due to malabsorption, due to vitD deficiency.

Question 12

Treatment for vitamin D deficiency in CKD:

Answer 12

1. Calcitriol (1,25-dihdroxycholecalciferol): provide active form of vitamin D2.

Ostelin (25-hydroxycholecalciferol): treat vitamin D deficiency due to inadequate intake or inadequate sun exposure. Ie. provide substrate for remaining endogenous enzymatic conversion.

Question 13

Vitamin D metabolism:

Answer 13

Vitamin D2 = ergocholecalciferol (plant sources)

Vitamin D3 = cholecalciferol (animal sources; 90% produced in skin exposed to UV light)(inactive, unhydroxylated form of vitamin D)

Calcidiol = hydroxylated form of D3 (25-hydroxycholecalciferol), produced by liver.

Calcitriol (1,25-dihydroxyvitamin D3) = active form of D3. Produced in kidneys by further hydroxylation of calcidiol.

Biosynthesis:
Cholecalciferol –> hydroxylated in the liver by enzyme vitamin D 25-hydroxylase, produced by hepatocytes –> 25-hydroxycholecalciferol (calcidiol or 25(OH)D) –> released into the plasma, bound to vitamin D-binding protein –> proximal tubules of the kidneys –> hydroxylated by the enzyme 25-hydroxyvitamin D3 1-alpha-hydroxylase –> calcitriol (1,25-dihydroxycholecalciferol and abbreviated to 1,25(OH)2D).

Levels of 1-alpha hydroxylase are increased by parathyroid hormone (and additionally by low calcium or phosphate).

Question 14

Treatment of hypercalcaemia in tertiary hyperparathyroidism:

Answer 14

• Calcitriol (suppressive) - but need to cease if increasing hypercalaemia
• Parathyroidectomy (best - if possible)
• Cinacalcet: calcimimetic (increases calcium sensing receptors (CaSR) in parathyroid gland) - used in patients who can’t tolerate parathyroidectomy

(Need to cease caltrate, as absorb some).

Question 15

Treatment of secondary hyperparathyroidism (hyperphosphataemia, hypocalcaemia)?Target?

Answer 15

• Calcitriol (suppressive)- Ostelin

Target: - Early CKD: aim PTH in normal range (maintaining normocalcaemia should do it)

• Advanced CKD: allow to increase to 2-3xULN

Question 16

Phosphate binders:

Answer 16

1. Caltrate (first line) - but use less than previous due to concerns about increasing calcium deposition in vessels
2. Alutabs - monitor levels 6/12 (maintain <1). Concerns about aluminium toxicity previously, but thought to be in dialysate (when water unfiltered).
3. Sevalamer - thought not to be absorbed. Some gut SEs
4. Lanthanum - thought not to be absorbed. Some gut SEs

Need to be taken with meals. Remember diet.

Consider dialysis if cannot achieve target with binders.

Question 17

Common complications of CKD:

Answer 17

• Renal anaemia- CKD-MBD- Hypertension- Volume overload- CVD- Hyperkalaemia (late CKD)

Question 18

Treating volume overload in CKD:

Answer 18

• Salt restriction- Fluid restriction- Diuretics- Dialysis

Question 19

Treatment of hyperkalaemia in CKD:

Answer 19

• Resonium (continuing ACEi if possible, for hyperproteinaemia)
• If ongoing hyperkalaemia may need to cease ACEi, continue resonium
• If still hyperkalaemic - consider dialysis

Question 20

Indications for haemodialysis in CKD:

Answer 20

1. Pericarditis
2. Fluid Overload Refractory to Medical Management
3. Electrolyte Disturbances Refractory to Medical Management
4. Accelerated Hypertension
5. Encephalopathy
6. Refractory Nausea and Vomiting
7. Declining Nutrition
8. Problematic Bleeding Diathesis

Important to note that the IDEAL trial showed no benefit in early dialysis versus late.

Question 21

How to manage hypertension in CKD? What is the target?

What is the guidelines that we use in Australia?

Answer 21

Target BP < 125/75 if proteinuria >1gm/24 hours

Target BP < 130/80 if proteinuria present, but 130/85 if NO proteinuria (0.25g/24) - may be easier to just remember 130/80 for all.

Question 22

Which agents are the best for hypertension in CKD?

Answer 22

If proteinuria: ACE/ARB
If IHD: beta blocker
If volume overload: diuretic
If diastolic dysfunction: CCB (This is new information!!!)

Question 23

What did the ON-TARGET study teach us about dual angiotensin blockade and renal disease?

Answer 23

It didn’t actually answer a question about renal disease. It answered a question about hypertension, particularly in cardiac patients.

Question 24

Why might erythropoeitin stimulation not work?

Answer 24

Multiple reasons.

1. insufficient dose
2. relative iron deficiency
3. alternative cause (e.g. bleeding; BM abnormality such as fibrosis from hyperPTH in adv CKD; BM abnor such as MDS)
4. chronic inflammatory state.
5. acquired antibody to EPO
6. acquired pure red cell aplasia (epprex - formula changed, so not really a thing anymore)
7. aluminium toxicity, previously associated with water supply

Question 25

what is the highest risk for mortality in dialysis patients?

cholesterol 6.0
bp 110/75
serum homocysteine 18 (N < 13)
BMI 36
serum TG 3.0

Answer 25

low blood pressure on dialysis is a bad thing

obesity is protective on dialysis (yup)

cholesterol/lipid management is an unanswered question, but statins are not started on dialysis (due to predominantly calcium based disease, not lipid based)